Rates of opioid use during pregnancy are at epidemic proportions. Neuroimaging suggests potential adverse effects of opioids on the developing brain. Children exposed to opioids in utero can have behavioral problems and lower school achievement and are also often exposed to toxic stress, maternal depression, and adverse home environments. It is important to determine the relative impacts of multiple adverse exposures and identify potentially modifiable factors. Our consortium, comprised of 4 highly performing centers of the NICHD Neonatal Research Network (NRN), proposes the Outcomes of Babies with Opioid Exposure (OBOE) study to quantify effects of prenatal opioid exposure on the trajectory of brain development, determine associations of neuroimaging parameters with developmental and behavioral outcomes, and examine how specific factors (differing substance exposures, severity of neonatal opioid withdrawal, maternal stress/ depression/ parenting) modify these effects. We hypothesize that neural connectivity and neuroanatomical volumes are altered by prenatal opioid exposure and that the magnitude of these alterations correlate with developmental and behavioral outcomes. To test this hypothesis, the consortium will enroll 200 opioid exposed infants and 75 healthy appropriately matched controls in a longitudinal cohort study. We anticipate enrolling approximately 75 infants (55 opioid exposed and 20 controls) in our clinical site at the University of Alabama at Birmingham. The Specific Aims are: Specific Aim 1: To determine the impact of prenatal opioid exposure on brain structure and connectivity over the first two years of life. Specific Aim 2: To define medical, developmental, and behavioral trajectories over the first 2 years of life in infants exposed to opioids. Specific Aim 3: To determine how the home environment, maternal mental health, and parenting modify trajectories of brain connectivity and neurodevelopment over the first two years of life. Our clinical site at the University of Alabama at Birmingham (UAB) is a Regional Perinatal Center that can enroll a large cohort of newborn infants both exposed and non-exposed to opioids in utero. A particular strength of UAB is the comprehensive addiction in pregnancy program (CAPP) that facilitates enrollment. As a participating center in the NICHD Neonatal Research Network, UAB has long-standing established and highly productive collaborations both with the other clinical centers in this application, and with the Administrative and Research Support Core at RTI International. Our center has an excellent track record of enrollment of high-risk infants in clinical studies with successful participant retention and follow-up to 2 years of age and beyond, with trained certified examiners for neurodevelopment as well as pediatric neuroradiologists and established infrastructure for neonatal and infant cranial magnetic resonance imaging.